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      Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization

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          Abstract

          During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

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          Cancer. p53, guardian of the genome.

          D P Lane (1992)
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            Cancer and Radiation Therapy: Current Advances and Future Directions

            In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
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              ATM and related protein kinases: safeguarding genome integrity.

              Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response--a cornerstone of genome stability--occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                14 January 2016
                January 2016
                : 17
                : 1
                : 102
                Affiliations
                Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany; Linda.Hartmann@ 123456web.de (L.H.); frederik.wenz@ 123456umm.de (F.W.); carsten.herskind@ 123456medma.uni-heidelberg.de (C.H.)
                Author notes
                [* ]Correspondence: patrick.maier@ 123456medma.uni-heidelberg.de ; Tel.: +49-621-383-3773; Fax: +49-621-383-3493
                Article
                ijms-17-00102
                10.3390/ijms17010102
                4730344
                26784176
                77bd00eb-3df2-4872-8402-1a2e5b89974b
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2015
                : 25 December 2015
                Categories
                Review

                Molecular biology
                radiotherapy,radioresistance,radiosensitization,double strand break,dna repair,apoptosis,mitotic catastrophe,senescence

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